2015
(Dec 23) Genome misfolding unearthed as new path to cancer [Defects of Hilbert-Fractal Clog "Proximity", see Figure above - Andras_at_Pellionisz_dot_com]
(Dec 22) The Fractal Brain and Fractal Genome [by bright layperson Wai h tsang]
(Dec 20) 2016 - The Genome Applicance; Taking the Genome Further in Healthcare
(Dec 15) Whole-Genome Analysis of the Simons Simplex Collection (SSC)
(Nov 25) The role of big data in medicine - Bringing together the right talent
(Oct 06) Researchers ID Copy Number Changes Associated With Cancer in Normal Cells
(Oct 05) Genome Pioneer: We Have The Dangerous Power To Control Evolution
(Sep 24) Genetic Analysis Supports Prediction That Spontaneous Rare Gene Mutations Cause Half Of All Autism Cases
(Sep 22) Sorry, Obama: Venter has no plans to share genomic data
(Sep 21) Google (NASDAQ: GOOG) Dips into Healthcare Business
(Sep 15) Head of Mental Health Institute Leaving for Google Life Sciences [Exodus from Government to Private Sphere]
(Sep 01) Bill Gates and Google back genome editing firm Editas
(Sep 01) Zephyr Health grabs $17.5M with infusion from Google Ventures
(Sep 01) Evolution 2.0 by Perry Marshall
(Aug 10) Genome researchers raise alarm over big data
(July 25) The case for copy number variations in autism
(July 25) Intricate DNA flips, swaps found in people with autism
(July 25) The mystery of the instant noodle chromosomes
(July 22) Can ‘jumping genes’ cause cancer chaos?
(July 21) Why you should share your genetic profile [the Noble Academic Dream and the Harsh Business Climate]
(July 20) Why James Watson says the ‘war on cancer’ is fighting the wrong enemy
(July 19) National Cancer Institute: Fractal Geometry at Critical Juncture of Cancer Research
(July 15) Apple may soon collect your DNA as part of a new ResearchKit program
(July 10) Sequencing the genome creates so much data we don’t know what to do with it
(July 07) The living realm depicted by the fractal geometry, (endorsement of FractoGene by Gabriele A. Losa)
(July 03) Google and Broad Institute Team Up to Bring Genomic Analysis to the Cloud
(June 19) GlaxoSmithKline, Searching For Hit Drugs, Pours $95M Into DNA 'Dark Matter'
(June 09) Recurrent somatic mutations in regulatory regions of human cancer genomes (Nature Genetics, dominant author Michael Snyder)
(May 22) Big Data (Stanford): 2015 Nobelist Michael Levitt (multi-scale biology) endorses the Fractal Approach to new school of genomics
(Apr 15) Eric Schadt - Big Data is revealing about the world’s trickiest diseases
(Apr 15) IBM Announces Deals With Apple, Johnson And Johnson, And Medtronic In Bid To Transform Health Care
(Apr 09) An 'evolutionary relic' of the genome causes cancer
(Mar 31) Time Magazine Cover Issue - Closing the Cancer Gap
(Mar 31) We have run out of money - time to start thinking!
(Mar 27) The Genome (both DNA and RNA) is replete with repeats. The question is the mathematics (fractals)
(Mar 21) On the Fractal Design in Human Brain and Nervous Tissue - Losa recognizes FractoGene
(Mar 16) Cracking the code of human life: The Birth of BioInformatics & Computational Genomics
(Feb 26) Future of Genomic Medicine Depends on Sharing Information - Eric Lander to Bangalore
(Feb 25) Genetic Geometry Takes Shape (and it is fractal, see FractoGene by Pellionisz, 2002)
(Feb 19) The $2 Trillion Trilemma of Global Precision Medicine
(Feb 11) BGI Pushing for Analytics
(Feb 10) Who was next to President Obama at the perhaps critical get-together (2011)?
(Feb 03) Round II of "Government vs Private Sector" - or "Is Our Understanding of Genome Regulation Ready for the Dreaded DNA Data Tsunami?"
(Jan 31) Houston, We've Got a Problem!
(Jan 27) Small snippets of genes may have big effect in autism
(Jan 27) Autism genomes add to disorder's mystery
(Jan 27) Hundreds of Millions Sought for Personalized Medicine Initiative
(Jan 22) SAP Teams with ASCO to Fight Cancer
(Jan 15) Human longevity-genentech ink deal sequence thousands genomes
(Jan 13) UCSC Receives $1M Grant from Simons Foundation to Create Human Genetic Variation Map
(Jan 12) Silencing long noncoding RNAs with genome-editing tools with full .pdf
(Jan 08) Who Owns the Biggest Biotech Discovery of the Century?
(Jan 07) NIH grants aim to decipher the language of gene regulation
(Jan 07) End of cancer-genome project prompts rethink: Geneticists debate whether focus should shift from sequencing genomes to analysing function
(Jan 07) Variation in cancer risk among tissues can be explained by the number of stem cell divisions

NIH grants aim to decipher the language of gene regulation

Bethesda, Md., Jan. 5, 2015 - The National Institutes of Health has awarded grants of more than $28 million aimed at deciphering the language of how and when genes are turned on and off. These awards emanate from the recently launched Genomics of Gene Regulation (GGR) program of the National Human Genome Research Institute (NHGRI), part of NIH.

"There is a growing realization that the ways genes are regulated to work together can be important for understanding disease," said Mike Pazin, Ph.D., a program director in the Functional Analysis Program in NHGRI's Division of Genome Sciences. "The GGR program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks. Such knowledge is important for defining the role of genomic differences in human health and disease."

With these new grants, researchers will study gene networks and pathways in different systems in the body, such as skin, immune cells and lung. The resulting insights into the mechanisms controlling gene expression may ultimately lead to new avenues for developing treatments for diseases affected by faulty gene regulation, such as cancer, diabetes and Parkinson's disease.

Over the past decade, numerous studies have suggested that genomic regions outside of protein-coding regions harbor variants that play a role in disease. Such regions likely contain gene-control elements that are altered by these variants, which increase the risk for a disease.

"Knowing the interconnections of these regulatory elements is critical for understanding the genomic basis of disease," Dr. Pazin said. "We do not have a good way to predict whether particular regulatory elements are turning genes off or activating them, or whether these elements make genes responsive to a condition, such as infection. We expect these new projects will develop better methods to answer these types of questions using genomic data."

[There is an interesting new scenario. This columnist (AJP; andras_at_pellionisz_dot_com) has devoted close to half a Century of very hard work to develop advanced geometrical understanding of the function of neural and genomic systems, as they arise from their so well known and so beloved structure. Geometrization (mathematization) of biology, however, is rather poorly received (when Mandelbrot was offered to lead, with very significant resources, declined the offer since "biologists were not ready"; Benoit upheld his proper impression through his life, as shown in his Memoirs).


End of cancer-genome project prompts rethink: Geneticists debate whether focus should shift from sequencing genomes to analysing function.

Nature, 2015 January 5.

A mammoth US effort to genetically profile 10,000 tumours has officially come to an end. Started in 2006 as a US$100-million pilot, The Cancer Genome Atlas (TCGA) is now the biggest component of the International Cancer Genome Consortium, a collaboration of scientists from 16 nations that has discovered nearly 10 million cancer-related mutations.

The question is what to do next. Some researchers want to continue the focus on sequencing; others would rather expand their work to explore how the mutations that have been identified influence the development and progression of cancer.

“TCGA should be completed and declared a victory,” says Bruce Stillman, president of Cold Spring Harbor Laboratory in New York. “There will always be new mutations found that are associated with a particular cancer. The question is: what is the cost–benefit ratio?”

Stillman was an early advocate for the project, even as some researchers feared that it would drain funds away from individual grants. Initially a three-year project, it was extended for five more years. In 2009, it received an additional $100 million from the US National Institutes of Health plus $175 million from stimulus funding that was intended to spur the US economy during the global economic recession.

The project initially struggled. At the time, the sequencing technology worked only on fresh tissue that had been frozen rapidly. Yet most clinical biopsies are fixed in paraffin and stained for examination by pathologists. Finding and paying for fresh tissue samples became the programme’s largest expense, says Louis Staudt, director of the Office for Cancer Genomics at the National Cancer Institute (NCI) in Bethesda, Maryland.

Also a problem was the complexity of the data. Although a few ‘drivers’ stood out as likely contributors to the development of cancer, most of the mutations formed a bewildering hodgepodge of genetic oddities, with little commonality between tumours. Tests of drugs that targeted the drivers soon revealed another problem: cancers are often quick to become resistant, typically by activating different genes to bypass whatever cellular process is blocked by the treatment.

Despite those difficulties, nearly every aspect of cancer research has benefited from TCGA, says Bert Vogelstein, a cancer geneticist at Johns Hopkins University in Baltimore, Maryland. The data have yielded new ways to classify tumours and pointed to previously unrecognized drug targets and carcinogens. But some researchers think that sequencing still has a lot to offer. In January, a statistical analysis of the mutation data for 21 cancers showed that sequencing still has the potential to find clinically useful mutations (M. S. Lawrence et al. Nature 505, 495–501; 2014).

On 2 December, Staudt announced that once TCGA is completed, the NCI will continue to intensively sequence tumours in three cancers: ovarian, colorectal and lung adenocarcinoma. It then plans to evaluate the fruits of this extra effort before deciding whether to add back more cancers.

Expanded scope

But this time around, the studies will be able to incorporate detailed clinical information about the patient’s health, treatment history and response to therapies. Because researchers can now use paraffin-embedded samples, they can tap into data from past clinical trials, and study how mutations affect a patient’s prognosis and response to treatment. Staudt says that the NCI will be announcing a call for proposals to sequence samples taken during clinical trials using the methods and analysis pipelines established by the TCGA.

The rest of the International Cancer Gene Consortium, slated to release early plans for a second wave of projects in February, will probably take a similar tack, says co-founder Tom Hudson, president of the Ontario Institute for Cancer Research in Toronto, Canada. A focus on finding sequences that make a tumour responsive to therapy has already been embraced by government funders in several countries eager to rein in health-care costs, he says. “Cancer therapies are very expensive. It’s a priority for us to address which patients would respond to an expensive drug.”

The NCI is also backing the creation of a repository for data not only from its own projects, but also from international efforts. This is intended to bring data access and analysis tools to a wider swathe of researchers, says Staudt. At present, the cancer genomics data constitute about 20 petabytes (1015 bytes), and are so large and unwieldy that only institutions with significant computing power can access them. Even then, it can take four months just to download them.

Stimulus funding cannot be counted on to fuel these plans, acknowledges Staudt. But cheaper sequencing and the ability to use biobanked biopsies should bring down the cost, he says. “Genomics is at the centre of much of what we do in cancer research,” he says. “Now we can ask questions in a more directed way.”

Nature 517, 128–129 (08 January 2015) doi:10.1038/517128a


Variation in cancer risk among tissues can be explained by the number of stem cell divisions

Cristian Tomasetti1,*, Bert Vogelstein2,*

Science 2 January 2015:

Vol. 347 no. 6217 pp. 78-81

DOI: 10.1126/science.1260825

- Author Affiliations

1Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 550 North Broadway, Baltimore, MD 21205, USA.

2Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA.

↵*Corresponding author. E-mail: ctomasetti@jhu.edu (C.T.); vogelbe@jhmi.edu (B.V.)

ABSTRACT

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

EDITOR'S SUMMARY

Crunching the numbers to explain cancer

Why do some tissues give rise to cancer in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by the number of stem cell divisions. By plotting the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, they found a strong correlation extending over five orders of magnitude. This suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development. Remarkably, this “bad luck” component explains a far greater number of cancers than do hereditary and environmental factors.

Cancer’s Random Assault

By DENISE GRADY

JAN. 5, 2015

New York Times

It may sound flippant to say that many cases of cancer are caused by bad luck, but that is what two scientists suggested in an article published last week in the journal Science. The bad luck comes in the form of random genetic mistakes, or mutations, that happen when healthy cells divide.

Random mutations may account for two-thirds of the risk of getting many types of cancer, leaving the usual suspects — heredity and environmental factors — to account for only one-third, say the authors, Cristian Tomasetti and Dr. Bert Vogelstein, of Johns Hopkins University School of Medicine. “We do think this is a fundamental mechanism, and this is the first time there’s been a measure of it,” said Dr. Tomasetti, an applied mathematician.

Though the researchers suspected that chance had a role, they were surprised at how big it turned out to be.

“This was definitely beyond my expectations,” Dr. Tomasetti said. “It’s about double what I would have thought.”

The finding may be good news to some people, bad news to others, he added.

Smoking greatly increases the risk of lung cancer, but for other cancers, the causes are not clear. And yet many patients wonder if they did something to bring the disease on themselves, or if they could have done something to prevent it.

“For the average cancer patient, I think this is good news,” Dr. Tomasetti said. “Knowing that over all, a lot of it is just bad luck, I think in a sense it’s comforting.”

Among people who do not have cancer, Dr. Tomasetti said he expected there to be two camps.

“There are those who would like to control every single thing happening in their lives, and for those, this may be very scary,” he said. “ ‘There is a big component of cancer I can just do nothing about.’

“For the other part of the population, it’s actually good news. ‘I’m happy. I can of course do all I know that’s important to not increase my risk of cancer, like a good diet, exercise, avoiding smoking, but on the other side, I don’t want to stress out about every single thing or every action I take in my life, or everything I touch or eat.’ ” Dr. Vogelstein said the question of causation had haunted him for decades, since he was an intern and his first patient was a 4-year-old girl with leukemia. Her parents were distraught and wanted to know what had caused the disease. He had no answer, but time and time again heard the same question from patients and their families, particularly parents of children with cancer.

“They think they passed on a bad gene or gave them the wrong foods or exposed them to paint in the garage,” he said. “And it’s just wrong. It gave them a lot of guilt.”

Dr. Tomasetti and Dr. Vogelstein said the finding that so many cases of cancer occur from random genetic accidents means that it may not be possible to prevent them, and that there should be more of an emphasis on developing better tests to find cancers early enough to cure them.

“Cancer leaves signals of its presence, so we just have to basically get smarter about how to find them,” Dr. Tomasetti said.

Their conclusion comes from a statistical model they developed using data in the medical literature on rates of cell division in 31 types of tissue. They looked specifically at stem cells, which are a small, specialized population in each organ or tissue that divide to provide replacements for cells that wear out.

Dividing cells must make copies of their DNA, and errors in the process can set off the uncontrolled growth that leads to cancer.

The researchers wondered if higher rates of stem-cell division might increase the risk of cancer simply by providing more chances for mistakes.

Dr. Vogelstein said research of this type became possible only in recent years, because of advances in the understanding of stem-cell biology.

Continue reading the main story

RECENT COMMENTS

John 6 hours ago

As my doctors told me, "You're the healthiest guy I've ever seen, except for that life-threatening cancer."

Tim Hunter 7 hours ago

Caused by chance really means "caused by a reason we do not yet understand". I firmly believe that when we live the way we do, surrounded by...

imperato 7 hours ago

So why does a blue whale containing the largest number of cells of any organism on the planet not have a correspondingly high cancer rate?

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The analysis did not include breast or prostate cancers, because there was not enough data on rates of stem-cell division in those tissues.

A starting point for their research was an observation made more than 100 years ago but never really explained: Some tissues are far more cancer-prone than others. In the large intestine, for instance, the lifetime cancer risk is 4.8 percent — 24 times higher than in the small intestine, where it is 0.2 percent.

The scientists found that the large intestine has many more stem cells than the small intestine, and that they divide more often: 73 times a year, compared with 24 times. In many other tissues, rates of stem cell division also correlated strongly with cancer risk.

Some cancers, including certain lung and skin cancers, are more common than would be expected just from their rates of stem-cell division — which matches up with the known importance of environmental factors like smoking and sun exposure in those diseases. Others more common than expected were linked to cancer-causing genes. To help explain the findings, Dr. Tomasetti cited the risks of a car accident. In general, the longer the trip, the higher the odds of a crash. Environmental factors like bad weather can add to the basic risk, and so can defects in the car.

“This is a good picture of how I see cancer,” he said. “It’s really the combination of inherited factors, environment and chance. At the base, there is the chance of mutations, to which we add, either because of things we inherited or the environment, our lifestyle.”

Dr. Kenneth Offit, chief of the clinical genetics service at Memorial Sloan Kettering Cancer Center in Manhattan, called the article “an elegant biological explanation of the complex pattern of cancers observed in different human tissues.”


Finding the simple patterns in a complex world (Barnsley: "Cancers are fractals")

An ANU mathematician has developed a new way to uncover simple patterns that might underlie apparently complex systems, such as clouds, cracks in materials or the movement of the stockmarket.

The method, named fractal Fourier analysis, is based on new branch of mathematics called fractal geometry.

The method could help scientists better understand the complicated signals that the body gives out, such as nerve impulses or brain waves.

"It opens up a whole new way of analysing signals," said Professor Michael Barnsley, who presented his work at the New Directions in Fractal Geometry conference at ANU.

"Fractal Geometry is a new branch of mathematics that describes the world as it is, rather than acting as though it's made of straight lines and spheres. There are very few straight lines and circles in nature. The shapes you find in nature are rough."

The new analysis method is closely related to conventional Fourier analysis, which is integral to modern image handling and audio signal processing.

"Fractal Fourier analysis provides a method to break complicated signals up into a set of well understood building blocks, in a similar way to how conventional Fourier analysis breaks signals up into a set of smooth sine waves," Professor Barnsley said.

Professor Barnsley's work draws on the work of Karl Weierstrass from the late 19th Century, who discovered a family of mathematical functions that were continuous, but could not be differentiated

"There are terrific advances to be made by breaking loose from the thrall of continuity and differentiability," Professor Barnsley said.

"The body is full of repeating branch structures – the breathing system, the blood supply system, the arrangement of skin cells, even cancer is a fractal."

[Michael Barnsley - with the founder of the field, Benoit Mandelbrot gone - is a paramount leader of both the mathematics of fractals, as well as its applications. Though the hitherto most lucrative application (fractal prediction of the obviously non-derivable stock-price curves) was not led by either of them (see Elliot Wave Theory), chances are that the required mathematical/algorithmic/software development will call for so significant investment, that "cloud computing companies" might spearhead or even monopolize the industry of FractoGene. Cloud computing provides the capital, infrastructure and the built-in capacity of enforcing royalties for algorithms run on myriads of their servers. 2015 is likely to be the year when the horse-race fully unfolds - andras_at_pellionisz_dot_com ]


A fractal geometric model of prostate carcinoma and classes of equivalence

[There is no need to read the poster - or the paper in print. Just looking at the Broccoli Romanesca (and the Hilbert fractal similarly widespread) will remind everyone by 2015 that "fractal genome grows fractal organisms" (FractoGene). What other concept grasps the essence of Recursive Genome Function? - Pellionisz_dot_com